Aminoacetonitriles have been prepared by reacting aldehydes with alkali metal cyanides followed by isolation of the cyanohydrin and subsequent reaction with ammonia in a suitable solvent. Isolation of the cyanohydrin can be difficult due to the solubility of cyanohydrin in aqueous medium. Moreover, isolation of the cyanohydrin is inconvenient and increases the risk of exposure to hydrogen cyanide.
Aminoacetonitriles have also been prepared without isolation of the cyanohydrin by the Strecker synthesis using an alkali metal cyanide and an ammonium salt under aqueous conditions. The Strecker synthesis, however, is not practical in cases where the aminoacetonitriles are subsequently used under nonaqueous conditions because it is difficult to isolate the aminoacetonitriles which are unstable and often water soluble.
In contrast, the present inventor has determined that cyanohydrins can be efficiently extracted into volatile water immiscible solvents such as ethyl acetate, thus, avoiding the problem of isolating the aminoacetonitriles. The solvent is removed to give the cyanohydrin, preferably as an oil, which is dissolved in a water miscible amide solvent and reacted with ammonia in the same vessel. Amide solvents are relatively involatile, thus, allowing passage of ammonia to occur over several hours without incurring significant solvent loss. Furthermore, clean conversion to the aminoacetonitriles occurs when amide solvents are used. The use of amide solvents allows the aminoacetonitriles to be converted to important intermediates such as thiadiazoles and acylamino derivatives. Other solvents are not as useful in these respects. For example, use of pyridine or acetonitrile as solvents in the amination step leads to the formation of by-products.
The process of the present invention for preparing aminoacetonitriles and thereafter thiadiazole derivatives is represented as follows. ##STR1## Reagents/solvents: (1) alkali metal cyanide, mineral acid, water, extract with water immiscible solvent; (2) amide solvent, ammonia; and (3) sulfur monochloride.